1. Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental Fig. S1

2. # # # Supplemental Fig. S2

3. Vinculin Actin Vinculin Actin Aβ42 O (µM) B - 0.25 2 - 0.25 2 2h 4h Cyto FC C ** * Tubulin Vinc Talin Tubulin Vinc Talin - + A FC Cyto Aβ42 O Supplemental Fig. S3 D APP/PS1WT Scale bar 30μm * * E * Focal Vinculin / Cytosolic Vinculin FC Vinculin (% Cont)

4. Cyto FC Aβ42 O - + + - - - + + Cof siR Cofilin P-Cof Vinculin Cofilin P-Cof Vinculin AB ** Supplemental Fig. S4 FC Vinc (% Cont)

5. NC (n=4)AD (n=5) Gender 2M & 2F2M & 3F Age Range 82-9582-96 Average Age (+SD) 88.75 + 6.7088.4 + 5.94 PMI Range (h) 3.87-8.63.0-7.8 Average PMI (+SD) 5.63 + 2.154.46 + 1.93 Supplemental Fig. S5

6. VehicleAβ42 O (1uM) Nox inhibitorHUTS-4MAB1965Vehicle H2DCF Supplemental Fig. S6 A

7. Aβ42 O +  1 IgG Aβ42 O Control Annexin V DAPI PI / DAPI B C * * H Control A  42 O A  42 O + MAB1965 PI D Supplemental Fig. S6 Continued

8. P-Cof Actin Aβ42 O - + + + Veh MAB1965Trolox IP: 14-3-3 SSH1 B Lysate Cof SSH1 Beads 14-3-3 Supplemental Fig. S7 A Aβ42 O C beads - - + Cof SSH1 IP: SSH1 Cof Lysate IP D ** Beads 14-3-3 IP: 14-3-3

9. Supplemental Fig. S8 Cofilin Actin WT Cofilin +/- HIPPO CTX WT GFAP DAPI PSD95 DAPI Synapsin I Cofilin+/- A DG CA1 CA3 Scale bar 300μm CA3 SL B